Project Summary Nearly 15 million transfusions are performed in the United States each year, with approximately 425,000 units transfused to pediatric patients alone. Despite the frequency ? transfusion procedures are not without risk. Blood transfusion complications may be attributed to heavy exposure to plastic devices, which are fabricated with chemicals that exert endocrine disrupting properties. The proposal's main hypothesis is that plastic devices are not universally biocompatible ? and that local and systemic reactions to chemical contaminants contribute to transfusion-related complications. The proposal's objective is to assess whether medical device biocompatibility and chemical exposures are underlying contributors to cardiovascular and autonomic dysfunction. The proposal also aims to identify safer biomaterials, chemicals and/or surface coatings for transfusion devices and blood banking. In this proposal, we will build upon our preliminary studies to address three specific aims: 1) To define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function, using in vivo and whole heart models. 2) To determine if biocompatibility and incidental chemical exposures are correlated with cardiovascular and autonomic abnormalities in transfused pediatric patients. 3) To compare and contrast alternative biomaterials, chemicals and fabrication techniques in order to identify safer replacements for transfusion-related devices. The proposed application will quantify the role of biocompatibility and chemical leaching on cardiovascular and autonomic function ? two targets that are highly susceptible to xenobiotic toxicity. If adverse outcomes are observed in the proposed study, it will pinpoint additional variables to monitor in future clinical investigations and epidemiological studies. Finally, this proposal aims to provide the foundation for objective decision making regarding the use of chemical additives with endocrine disrupting properties in medical device manufacturing by scientific, medical and regulatory communities. Results of the proposed studies can incentivize and accelerate the development and clinical adoption of alternative biomaterials, additives and/or fabrication techniques to improve transfusion patient safety.